The objective of this research proposal is to investigate the contribution of a reticuloendothelial depressing substance to the reticuloendothelial system (RES) depression during clinical and experimental shock states. The RES functions as an important host-defense mechanism during shock and the failure of this system may be important in the pathogenesis of irreversible shock. RE depressing substance was first described by Blattberg and Levy as a low molecular weight peptide which is capable of depressing RES phagocytic function and increasing the susceptibility to experimental shock. The proposed experiments will evaluate the presence of RE depressing substance in clinical and experimental shock states, and will relate the levels of RE depressing substance to the degree of RES depression during experimental shock. Further, the preparation of RE depressing substance from the plasma of animals in shock will allow the evaluation of the effects of this substance on survival following experimental shock, as well as the evaluation of the mechanism of action in terms of the effects on factors that may contribute to the RES depression during shock, i.e., hepatic blood flow, hepatic Kupffer cell function and circulating activity of opsonic protein (alpha-2-glycoprotein). It will also be possible to evaluate the effectiveness of the administration of purified opsonic protein as a potential means of reversing the effects of RE depressing substance. Additionally, the similarities between RE depressing substance and myocardial depressing factor will be studied.